Biomarkers of advanced prostate cancer in Nigerians using the Decipher^R Assay

 

         Dr Samaila I Shuaibu (FWACS)

              Division of Urology, Jos University Teaching Hospital, Jos

A Research proposal submitted to STAMINA,

                      July, 2016

  Biomarkers of advanced prostate cancer in Nigerians using the Decipher^R Assay.

ABSTRACT

Introduction

Prostate cancer prevalence was previously perceived to be low in Africa.  Recent studies however, show that Nigerian men have a prevalence  of 127- 182.5/100,000.¹ These figures approach that of African American and Jamaicans.² Most  Nigerian men with prostate cancer  present late with 88.9% and 92.4% having locally advanced or metastatic disease in Ilorin(North Central Nigeria) and Ife(Western Nigeria) respectively  and these patients subsequently die of the disease.^1,3

Consequently, much effort is being placed on detecting prostate cancer in an early, curable stage to decrease the rate of mortality from this disease. Along with genetics, social and environmental factors (especially diet and lifestyle) may act as the determining factors, which may explain why some individuals are at higher risk for developing prostate cancer than are others. Nevertheless, in most cases, this disease can be treated effectively and even eradicated when the disease is detected at a very early stage. ⁴

A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.^5-7 a biomarker reveals further information to existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for   individual patients. The form of prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues. Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. Better cancer biomarkers have the potential to improve diagnosis, treatment strategy, disease monitoring and prediction of treatment success⁸

 

Currently the biomarkers of advanced cancer of the prostate in patients of sub-Saharan Africa have not been well characterised. This study aims to determine the genetic biomarkers of advanced prostate cancer in Nigerians and assess the clinic pathologic attributes of advanced prostate cancer in 2 tertiary health care centres in North central and North-western Nigeria.   

Methods:

This will be a retrospective crossectional study. Hospital records of all prostate cancer patients diagnosed at the Jos University Teaching Hospital and Ahmadu Bello University Teaching Hospital from 2011 -2015 will be retrieved. Thereafter clinical features of these patients and pathological characteristics of prostate cancer will be extracted. These will include Age, BMI, History and duration of Cigarette smoking and alcohol consumption. Family History of prostate cancer.  Gleason Score and clinical stage of tumour. Using the AJCC-TNM Staging (2009), patients with T3 Any N Any M will be classified as advanced prostate carcinoma. Archived blocks of needle biopsies of patients with advanced prostate carcinoma will be retrieved from the histopathology departments of the Teaching Hospitals and subsequently analysed using the Decipher^R Assay (Genome Dx) to assess the Biomarkers of advanced carcinoma of the prostate. This will be done at the San Diego laboratory of Genome Dx, California, USA.

Using Phone contacts from the records, tracing of patients will be done to determine those who are alive and those who have died. Kaplan Meier survival analysis will be carried out.

Results will be analysed using SPSS version 16 and presented as tables and figures. P value < 0.05 will be taken as statistically significant.

Budget

Sample size 50 Specimen

Personnel

Principal Investigators

 

Dr S.I Shuaibu (Jos University Teaching Hospital) - Principal investigator           

Dr Ahmed Mohammed (Ahmadu Bello University Teaching Hospital)  

Dr Adam Murphy                                                                   Mentor  

Prof NK Dakum                                                          

 Prof BM Mandong                                                     

Prof VM Ramyil                                                                                

Dr CG Ofoha                                                                                       

Dr IC Akpayak                                                                                    

 Dr D.  Ayuba                                                                          

Dr C Agbo                                                                             

Dr V E Onowa                                                                       

Dr L E Nabasu                                                                       

Dr Z Gallam                                                               

Rick Kittles, PhD

Department of Urology

University of Arizona Cancer Center

1515 N. Campbell Avenue

P.O. Box 245024

Tucson, AZ 85724

Office: (520) 626-8003

Email: rkittles@surgery.arizona.edu

Budget justification

1. Dr Samaila I Shuaibu is the Principal Investigator who is mentored by Dr. Adam Murphy and has been engaging in clinical research focused on prostate cancer.
2. Muhammed Ahmed is a Consultant Urologist at the ABU Teaching hospital and will supervise the research at the Ahamadu Bello University Teaching Hospital.
3. Dr Adam Murphy - Mentor: Dr. Murphy is an Assistant Professor of Urology at North-western Urologist. He is an academic urologist focused on health disparities research in prostate cancer. He has spent a three-year research fellowship in Dr. Rick Kittles’ laboratory focused on the genetics of prostate cancer risk in African Americans and health disparities research. He has led several multi-site clinical studies on prostate cancer including grant funded studies from the Centers for AIDS for prostate cancer treatment and incidence disparities in HIV positive men, and a VA Career Development Award and a Department of Defence award on vitamin D’s role in aggressive prostate cancer. He is co-PI on a DOD grant and PI on an R21, which features faculty from 5 academic and public institutions. He is a mentor on the STAMINA D43 grant for non-HIV related malignancies for several junior faculty members. He will be involved in all aspects of this protocol and has effectively collaborated across disciplines and institutions for high-impact studies.
4. Prof NK Dakum is a Consultant Urologist who will be involved in reviewing the manuscript and analysis for intellectual content.
5. Professor Venyir  Ramyil  is a Consultant Urologist who will be involved in data analysis
6. Barnabas Mandong is a Histopathologist and they will be responsible for intellectual content and critical review of the manuscript. .
7. Dr   Chimaobi Ofoha is a Consultant Urologists and will be involved in data review and analysis.
8. Dr. Idorenyin  Akpayak is a Consultant Urologists and will be involved in data review and analysis.
9. Dr Ayuba is a Histopathologist at JUTH and will be involved in Tissue block retrieval, pathologic review of specimen.

 

i. Specific aims;

1. To determine the genetic biomarkers of advanced prostate cancer in Nigerians using the Decipher ^R Assay
2. To determine the clinical risk factors for advanced  prostate cancer  in Nigerians
3. To determine the survival duration of patients with advanced prostate cancer in Nigeria.

 

References:

1.  Badmus TA, Adesukami AR, Yusuf BM, Oseni GO, Eziyi AK, Bakare T et al. Burden of Prostate Cancer in South Western Nigeria.Urology.2010 Aug;76(2):412-6.
2.  Osegbe DN. Prostate cancer in Nigerians: Facts and non-facts. J Urol 1997; 157: 1340-3.
3. Ajape AA, Ibrahim KO, Fakeye JA, Abiola OO. An overview of cancer of the prostate diagnosis and management in Nigeria. The experience in a Nigerian tertiary hospital. Ann Afr Med. 2010;9:113-7

 

4. Prostate Cancer Foundation. Home page of Prostate Cancer Foundation. http://www.prostatecancerfoundation.org Accessed 2/4/2016
5. Atkinson AJJr, Colburn WA, DeGruttola VG, DeMets DL, et al. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Biomarkers Definitions Working Group. Clinical Pharmacol & Therapeutics 2001; 69: 89–95.
6.  Woodcock J. A Framework for Biomarker and Surrogate Endpoint Use in Drug Development. http://www.fda.gov/ohrms/dockets/ac/04/slides/2004 4079S2_03_Woodcock.ppt. accessed 2/4/2016
7.  [Internet] National Cancer Institute.                                                                         Dictionary of Cancer Terms. http://www.cancer.gov/dictionary   accessed 2/4/2016.
8. Bhatt, A., Mathur, R., Farooque, A., Verma, A.  Dwarakanath, B. Cancer biomarkers – current perspectives. Indian J Med Res 2010: 132: 129–149.

vi. Plan for protection of patient information:

 Patient’s information will be entered in a coded form in a lap top which will be accessed only by the Principal Investigator.